Objective: Drug resistance remains a major challenge in prostate cancer treatment, reducing the efficacy of docetaxel. Identifying natural agents that can enhance the response to chemotherapy is of growing interest. This study aimed to evaluate the antioxidant, antiproliferative, apoptosis-inducing, and chemosensitizing effects of the aerial parts of Thymus vulgaris hydroalcoholic extract and its major monoterpene phenol, thymol, on prostate cancer cells.
Materials and Methods: The hydroalcoholic extract was phytochemically characterized, and its antioxidant activity was measured via DPPH and ABTS assays. Prostate cancer (LNCaP) and normal fibroblast cell lines were treated with the extract, thymol, and their combination with docetaxel. Cell viability (MTT), apoptosis (TUNEL, Annexin V/PI, and DNA fragmentation), mitochondrial membrane potential (JC-1), and cytochrome C levels were assessed. Gene expression levels of Bax, Bcl-2, p53, and caspase-3 were quantified using RT-PCR. The combination index (CI) and dose reduction index (DRI) were also calculated.
Results: The extract contained polyphenols, flavonoids, alkaloids, and saponins and showed antioxidant activity. Both extract and thymol selectively reduced prostate cancer cell viability (IC₅₀: 44.6 and 16.7 µg/ml, respectively) while sparing normal fibroblasts. Apoptosis was confirmed by DNA fragmentation, increased Bax, caspase-3, and p53 expression, loss of mitochondrial membrane potential, and elevated cytochrome C release. Combination with docetaxel resulted in synergistic cytotoxicity (CI<1) and substantial dose reduction for both agents (DRI >1).
Conclusion: Thymus vulgaris extract and thymol exhibit selective anticancer activity and enhance docetaxel efficacy in vitro. These findings highlight their potential as adjunct agents in prostate cancer therapy, although further in vivo validation is required.