Alkaloids mediated regulation of microRNA in cancer: molecular insights and emerging therapeutic strategies

Cancer, the second leading cause of death worldwide, has prompted extensive research to uncover its mechanisms and identify effective prognostic and therapeutic strategies. Deregulation of microRNAs (miRNAs) contributes to the abnormal activation of tumorigenic processes and repression of tumor-suppressive mechanisms across various cancer types. Plants biosynthesize a wide range of structurally diverse secondary metabolites with outstanding medicinal applications. Despite notable advancements in cancer therapeutics, the current anticancer drugs and treatment approaches have not achieved complete effectiveness. The literature indicates that alkaloids and their derivatives possess strong anticancer potential and have emerged as promising pharmacological agents. Numerous alkaloids screened from herbal (medicinal) sources have demonstrated significant antiproliferative and anticancer effects against several cancer types. Numerous anticancer drugs derived from alkaloids, including vindesine, vinblastine, vincristine, and vinorelbine, have been developed and are widely used in cancer therapeutics. Research has also shown that the alkaloid regulates miRNA expression, thereby inhibiting cancer cell invasion and migration, and leading to apoptosis induction. This review comprehensively evaluated the role of alkaloids in regulating miRNA expression and their downstream targets involved in cancer progression, metastasis, and chemoresistance in various carcinomas. We highlight how miRNAs function as key regulators and mediators of the anticancer mechanisms of these natural compounds. Furthermore, we have also summarized the potent role of different types of miRNAs in cancer progression and development.