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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

A schematic representation describing the anti-proliferation activities of SQ40 in regulation of cell cycle proteins in LNCaP cells.
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pone.0121752.g009: A schematic representation describing the anti-proliferation activities of SQ40 in regulation of cell cycle proteins in LNCaP cells.

Mentions: Results from the present study showed that SQ40 induced selective cytotoxicity on human prostate cancer cells and inhibited the growth of LNCaP cells. SQ40 was shown to down-regulate the expression levels of G1-to-S phase transition regulatory proteins, Cyclin D1, CDK4 and CDK2 and up-regulate Cyclin inhibitor protein, p21Waf1/Cip1 which subsequently led to cell cycle arrest in G0/G1 phase (Fig. 9). Growth inhibition induced by SQ40 is associated with the inhibition of AR activities in parts as shown by the suppression of AR translocation into the nucleus from cytoplasm and reduction of the secretion of PSA by treatment of SQ40 in the presence of DHT stimulation. In addition, the anti-tumorigenic activity of SQ40 was successfully demonstrated in mouse xenograft model.


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)

A schematic representation describing the anti-proliferation activities of SQ40 in regulation of cell cycle proteins in LNCaP cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0121752.g009: A schematic representation describing the anti-proliferation activities of SQ40 in regulation of cell cycle proteins in LNCaP cells.
Mentions: Results from the present study showed that SQ40 induced selective cytotoxicity on human prostate cancer cells and inhibited the growth of LNCaP cells. SQ40 was shown to down-regulate the expression levels of G1-to-S phase transition regulatory proteins, Cyclin D1, CDK4 and CDK2 and up-regulate Cyclin inhibitor protein, p21Waf1/Cip1 which subsequently led to cell cycle arrest in G0/G1 phase (Fig. 9). Growth inhibition induced by SQ40 is associated with the inhibition of AR activities in parts as shown by the suppression of AR translocation into the nucleus from cytoplasm and reduction of the secretion of PSA by treatment of SQ40 in the presence of DHT stimulation. In addition, the anti-tumorigenic activity of SQ40 was successfully demonstrated in mouse xenograft model.

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