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The in vitro and in vivo anti-cancer activities of a standardized quassinoids composition from Eurycoma longifolia on LNCaP human prostate cancer cells.

Tong KL, Chan KL, AbuBakar S, Low BS, Ma HQ, Wong PF - PLoS ONE (2015)

Bottom Line: Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family.Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line.Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family. They are also the major bioactive compounds found in Eurycoma longifolia which is commonly used as traditional medicine in South East Asia to treat various ailments including sexual dysfunction and infertility. These uses are attributed to its ability to improve testosterone level in men. Chronic consumption of E. longifolia extracts has been reported to increase testosterone level in men and animal model but its effect on prostate growth remains unknown. Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC50 value of 5.97 μg/mL while the IC50 on RWPE-1 human prostate normal cells was 59.26 μg/mL. SQ40 also inhibited 5α-dihydrotestosterone-stimulated growth in LNCaP cells dose-dependently. The inhibitory effect of SQ40 in anchorage-independent growth of LNCaP cells was also demonstrated using soft agar assay. SQ40 suppressed LNCaP cell growth via G0/G1 phase arrest which was accompanied by the down-regulation of CDK4, CDK2, Cyclin D1 and Cyclin D3 and up-regulation of p21Waf1/Cip1 protein levels. SQ40 at higher concentrations or longer treatment duration can cause G2M growth arrest leading to apoptotic cell death as demonstrated by the detection of poly(ADP-ribose) polymerase cleavage in LNCaP cells. Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment. In addition, intraperitoneal injection of 5 and 10 mg/kg of SQ40 also significantly suppressed the LNCaP tumor growth on mouse xenograft model. Results from the present study suggest that the standardized total quassinoids composition from E. longifolia promotes anti-prostate cancer activities in LNCaP human prostate cancer cells.

No MeSH data available.


Related in: MedlinePlus

Growth profile of LNCaP and RWPE-1 cells upon treatment with SQ40.The growth kinetics of (A) LNCaP and (B) RWPE-1 cells were examined real-time using RTCA. The impedance values were recorded in real-time and were expressed as the Cell Index (CI). Cells treated with growth media alone were referred as vehicle control while 5 μM paclitaxel-treated cells were referred as positive control. (C) SQ40-treated LNCaP cells were stained with 0.4% trypan blue solutions in a ratio of 1:1 after 72 and 96 hours of treatment respectively. Cells treated with growth media alone were referred as vehicle control while 1 μM paclitaxel-treated cells were referred as positive control. Data were expressed as means ± SEM of three independent experiments. ** indicates p<0.01 versus 72-hour treated vehicle control. ## indicates p<0.01; ###, p<0.001 versus 96-hour treated vehicle control.
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pone.0121752.g004: Growth profile of LNCaP and RWPE-1 cells upon treatment with SQ40.The growth kinetics of (A) LNCaP and (B) RWPE-1 cells were examined real-time using RTCA. The impedance values were recorded in real-time and were expressed as the Cell Index (CI). Cells treated with growth media alone were referred as vehicle control while 5 μM paclitaxel-treated cells were referred as positive control. (C) SQ40-treated LNCaP cells were stained with 0.4% trypan blue solutions in a ratio of 1:1 after 72 and 96 hours of treatment respectively. Cells treated with growth media alone were referred as vehicle control while 1 μM paclitaxel-treated cells were referred as positive control. Data were expressed as means ± SEM of three independent experiments. ** indicates p<0.01 versus 72-hour treated vehicle control. ## indicates p<0.01; ###, p<0.001 versus 96-hour treated vehicle control.

Mentions: Growth kinetics of LNCaP and RWPE-1 cells were monitored in real-time using an impedance-based cell sensing measurement system. It was observed that the normalized CI values for SQ40-treated LNCaP cells showed a steady decline after 6 hours of treatment with the quassinoids composition. After 72 hours of treatment, it was observed that the LNCaP cells treated with lower concentrations (2.5–10 μg/mL) of SQ40 only scored about half of the normalized CI values of vehicle control cells and this suggests that SQ40 at low concentrations exerts cytostatic effect on LNCaP cells. However, SQ40 at higher concentrations (20–80 μg/mL) resulted in very low normalized CI values similar to that of the positive control, 5 μM paclitaxel-treated cells (Fig. 4A).


The in vitro and in vivo anti-cancer activities of a standardized quassinoids composition from Eurycoma longifolia on LNCaP human prostate cancer cells.

Tong KL, Chan KL, AbuBakar S, Low BS, Ma HQ, Wong PF - PLoS ONE (2015)

Growth profile of LNCaP and RWPE-1 cells upon treatment with SQ40.The growth kinetics of (A) LNCaP and (B) RWPE-1 cells were examined real-time using RTCA. The impedance values were recorded in real-time and were expressed as the Cell Index (CI). Cells treated with growth media alone were referred as vehicle control while 5 μM paclitaxel-treated cells were referred as positive control. (C) SQ40-treated LNCaP cells were stained with 0.4% trypan blue solutions in a ratio of 1:1 after 72 and 96 hours of treatment respectively. Cells treated with growth media alone were referred as vehicle control while 1 μM paclitaxel-treated cells were referred as positive control. Data were expressed as means ± SEM of three independent experiments. ** indicates p<0.01 versus 72-hour treated vehicle control. ## indicates p<0.01; ###, p<0.001 versus 96-hour treated vehicle control.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4380335&req=5

pone.0121752.g004: Growth profile of LNCaP and RWPE-1 cells upon treatment with SQ40.The growth kinetics of (A) LNCaP and (B) RWPE-1 cells were examined real-time using RTCA. The impedance values were recorded in real-time and were expressed as the Cell Index (CI). Cells treated with growth media alone were referred as vehicle control while 5 μM paclitaxel-treated cells were referred as positive control. (C) SQ40-treated LNCaP cells were stained with 0.4% trypan blue solutions in a ratio of 1:1 after 72 and 96 hours of treatment respectively. Cells treated with growth media alone were referred as vehicle control while 1 μM paclitaxel-treated cells were referred as positive control. Data were expressed as means ± SEM of three independent experiments. ** indicates p<0.01 versus 72-hour treated vehicle control. ## indicates p<0.01; ###, p<0.001 versus 96-hour treated vehicle control.
Mentions: Growth kinetics of LNCaP and RWPE-1 cells were monitored in real-time using an impedance-based cell sensing measurement system. It was observed that the normalized CI values for SQ40-treated LNCaP cells showed a steady decline after 6 hours of treatment with the quassinoids composition. After 72 hours of treatment, it was observed that the LNCaP cells treated with lower concentrations (2.5–10 μg/mL) of SQ40 only scored about half of the normalized CI values of vehicle control cells and this suggests that SQ40 at low concentrations exerts cytostatic effect on LNCaP cells. However, SQ40 at higher concentrations (20–80 μg/mL) resulted in very low normalized CI values similar to that of the positive control, 5 μM paclitaxel-treated cells (Fig. 4A).

Bottom Line: Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family.Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line.Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family. They are also the major bioactive compounds found in Eurycoma longifolia which is commonly used as traditional medicine in South East Asia to treat various ailments including sexual dysfunction and infertility. These uses are attributed to its ability to improve testosterone level in men. Chronic consumption of E. longifolia extracts has been reported to increase testosterone level in men and animal model but its effect on prostate growth remains unknown. Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC50 value of 5.97 μg/mL while the IC50 on RWPE-1 human prostate normal cells was 59.26 μg/mL. SQ40 also inhibited 5α-dihydrotestosterone-stimulated growth in LNCaP cells dose-dependently. The inhibitory effect of SQ40 in anchorage-independent growth of LNCaP cells was also demonstrated using soft agar assay. SQ40 suppressed LNCaP cell growth via G0/G1 phase arrest which was accompanied by the down-regulation of CDK4, CDK2, Cyclin D1 and Cyclin D3 and up-regulation of p21Waf1/Cip1 protein levels. SQ40 at higher concentrations or longer treatment duration can cause G2M growth arrest leading to apoptotic cell death as demonstrated by the detection of poly(ADP-ribose) polymerase cleavage in LNCaP cells. Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment. In addition, intraperitoneal injection of 5 and 10 mg/kg of SQ40 also significantly suppressed the LNCaP tumor growth on mouse xenograft model. Results from the present study suggest that the standardized total quassinoids composition from E. longifolia promotes anti-prostate cancer activities in LNCaP human prostate cancer cells.

No MeSH data available.


Related in: MedlinePlus