Anticancer Assessment of Wild Taxus Wallichiana Bark-Derived Novel Taxane Analogues Targeting Breast, Ovarian, and Lung Malignancies

Cancer continues to be a major global health challenge and remains one of the leading causes of death worldwide. Among the various cancer types, breast, ovarian, and lung cancers contribute significantly to cancer-related morbidity and mortality. Although considerable progress has been achieved in cancer diagnosis and treatment, the effectiveness of current therapies is often limited by drug resistance, tumor heterogeneity, adverse side effects, and disease recurrence. Taxanes, particularly paclitaxel and docetaxel, are among the most widely used anticancer agents because of their ability to stabilize microtubules, disrupt cell division, and induce programmed cell death. Nevertheless, challenges such as multidrug resistance, toxicity, and limited natural resources have encouraged the search for novel taxane-based compounds with improved therapeutic potential. Taxus wallichiana Zucc. (Himalayan yew) is a medicinally valuable conifer and an important natural source of taxane diterpenoids. Despite its recognized pharmaceutical significance, many taxane constituents present in this species remain inadequately explored. Therefore, the present study aimed to isolate novel taxane analogues from the bark of wild T. wallichiana and evaluate their anticancer activity against breast (MCF-7), ovarian (SKOV-3), and lung (A549) cancer cell lines. The isolated compounds were characterized using chromatographic and spectroscopic techniques and subsequently assessed through in vitro cytotoxicity assays, morphological observations, and molecular docking studies targeting β-tubulin. The findings demonstrated a concentration-dependent reduction in cancer cell viability, with the strongest inhibitory effects observed against SKOV-3 ovarian cancer cells. Treated cells exhibited characteristic apoptotic features, including cell shrinkage, membrane blebbing, and reduced colony-forming ability. Molecular docking analysis further revealed strong binding interactions between the isolated taxane analogues and the β-tubulin active site, indicating a mechanism of action similar to that of paclitaxel. Overall, the study suggests that bark-derived taxane analogues from T. wallichiana possess promising anticancer properties and may serve as potential candidates for the development of next-generation taxane-based therapeutics. Further in vivo investigations and preclinical studies are recommended to validate their efficacy and safety.