3-ACETYL-11-KETO-β-BOSWELLIC ACID (AKBA) SYNERGISTICALLY ENHANCED 5-FU-INDUCED ANTIPROLIFEATIVE AND APOPTOTIC ACTIVITY IN ANDROGEN INDEPENDENT PROSTATE CANCER CELLS.

Verma, Mahima; Fatima, Shireen; Ansari, Irfan Ahmad

Studies on the results of merging cutting-edge plant-derived phytochemicals with cytostatic drugs used in cancer therapy have drawn a lot of attention recently. Several chemotherapeutic agents are documented to develop resistance over time and exhibit significant side effects. To enhance effectiveness and mitigate drug-induced toxicity, a range of bioactive compounds have been employed either independently or in conjunction with conventional chemotherapy. Consequently, this study investigates the potential of AKBA to inhibit the proliferation of Prostate cancer (PrCa) cells when combined with 5-FU. The isobolograms of the combination treatment demonstrated potential of AKBA to synergistically augment the cytotoxic potency of 5-FU in DU145 cells with CI value <1 at all tested combinations as compared to the untreated control cells. Morevoer, combined treatment of AKBA and 5-FU led to significantly increased cellular alterations in DU145 PrCa cells. Moreover, DAPI/PI merge staining showed enhanced nuclear damage in PrCa cells caused by combination treatment. Similarly, increased ROS generation and mitochondrial membrane depolarization were also found in PrCa cells when treated in combination with AKBA and 5-FU. These findings collectively signify an enhanced cytotoxic effect of 5-FU at lower doses when combined with AKBA, resulting in elevated levels of oxidative stress, mitotic catastrophe, and apoptosis. Based on the findings of this study, the combined effects of AKBA and 5-FU may result in an intriguing approach to minimize the menace of high doses of chemotherapeutic drugs. AKBA is thus recommended as a prospective and promising therapeutic adjunct for the prevention and treatment of cancer.

PROSTATE cancer; ANTINEOPLASTIC agents; ANDROGEN receptors; MITOCHONDRIAL membranes; ANDROGENS; BIOACTIVE compounds

Biochemical & Cellular Archives, 2024, Vol 24, Issue 1, p1193

0972-5075

Academic Journal

10.51470/bca.2024.24.1.1193