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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

The effects of SQ40 on LNCaP cells anchorage-independent growth.LNCaP cells were pre-treated with SQ40 or vehicle control for 72 hours and then plated on the soft agar media for another 3 weeks. Representative colonies of (A) vehicle control and (B) SQ40-treated LNCaP cells are shown. (C) Graphical representations of soft agar colony formation efficiency. Data were expressed as mean ± SEM of three independent experiments for vehicle control cells and six independent experiments for SQ40-treated cells. * indicates p<0.05 versus vehicle control.
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pone.0121752.g003: The effects of SQ40 on LNCaP cells anchorage-independent growth.LNCaP cells were pre-treated with SQ40 or vehicle control for 72 hours and then plated on the soft agar media for another 3 weeks. Representative colonies of (A) vehicle control and (B) SQ40-treated LNCaP cells are shown. (C) Graphical representations of soft agar colony formation efficiency. Data were expressed as mean ± SEM of three independent experiments for vehicle control cells and six independent experiments for SQ40-treated cells. * indicates p<0.05 versus vehicle control.

Mentions: The effect of SQ40 on LNCaP cells anchorage-independent growth was investigated using soft agar assay. The LNCaP cells were pre-treated with SQ40 at its IC50 value for 3 days prior to plating on the soft agar media at an equal cell number with the vehicle control cells. The size of quassinoids composition-treated cell colonies was markedly reduced compared to the vehicle control cell colonies (Fig. 3A and 3B). In addition, the colony formation efficiency of SQ40-treated LNCaP cells was significantly reduced when compared to the vehicle control (Fig. 3C; p<0.05). This finding suggests that SQ40 inhibited anchorage-independent growth of LNCaP prostate cancer cells.


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)

The effects of SQ40 on LNCaP cells anchorage-independent growth.LNCaP cells were pre-treated with SQ40 or vehicle control for 72 hours and then plated on the soft agar media for another 3 weeks. Representative colonies of (A) vehicle control and (B) SQ40-treated LNCaP cells are shown. (C) Graphical representations of soft agar colony formation efficiency. Data were expressed as mean ± SEM of three independent experiments for vehicle control cells and six independent experiments for SQ40-treated cells. * indicates p<0.05 versus vehicle control.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0121752.g003: The effects of SQ40 on LNCaP cells anchorage-independent growth.LNCaP cells were pre-treated with SQ40 or vehicle control for 72 hours and then plated on the soft agar media for another 3 weeks. Representative colonies of (A) vehicle control and (B) SQ40-treated LNCaP cells are shown. (C) Graphical representations of soft agar colony formation efficiency. Data were expressed as mean ± SEM of three independent experiments for vehicle control cells and six independent experiments for SQ40-treated cells. * indicates p<0.05 versus vehicle control.
Mentions: The effect of SQ40 on LNCaP cells anchorage-independent growth was investigated using soft agar assay. The LNCaP cells were pre-treated with SQ40 at its IC50 value for 3 days prior to plating on the soft agar media at an equal cell number with the vehicle control cells. The size of quassinoids composition-treated cell colonies was markedly reduced compared to the vehicle control cell colonies (Fig. 3A and 3B). In addition, the colony formation efficiency of SQ40-treated LNCaP cells was significantly reduced when compared to the vehicle control (Fig. 3C; p<0.05). This finding suggests that SQ40 inhibited anchorage-independent growth of LNCaP prostate cancer cells.

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