Immunomodulatory lectin from Cordia myxa targets PI3K/AKT signalling mediated apoptosis to regress both in-vitro and in-vivo tumour

• Published in: International journal of biological macromolecules 2025-03, Vol.294, p.139433, Article 139433
• Main Authors: Siddesh, B.M., Kiran, B.K., Sherapura, Ankith, Banumathi, Mahmood, Riaz, Suchetha Kumari, N., Prabhakar, B.T.
• Format: Article
• Language: English
• Subjects: Apoptosis; Cordia myxa; Immunomodulation; Lectins; PI3K/AKT and antitumor
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.139433

Plant based medicine is gaining recognition as a complementary approach to conventional treatments. Plants contain lectins that bind to carbohydrates and exhibit various biological properties and being used in cancer treatment. In present investigation Cordia myxa fruit was chosen, screen for presence of lectin and explore its biological role. Screening of lectin was conducted through HA activity. Purification and characterization through conventional methods. HI assay to confirm the carbohydrate specificity. Immunomodulatory role by proliferative assays and ELISA. Apoptosis by annexin-V stain, TUNEL, MOMP and COMET assay and in-vivo antitumour activity by EAC induced ascites and solid tumour model. Gene expression through IB and IHC. The results illustrated that, presence of immunostimulant, ̴12 kDa lectin (CML) with strong leucoaggulutination activity having ovalbumin & fetuin specificity. The CML exhibits immune cell proliferation and secretes immune cytokines IL-2, IL-10 & IL-12. The immunomodulatory experiments infer that, CML induces anti-proliferative response against A549 and EAC by inducing apoptosis, which were validated in an in-vitro &in-vivo models. Mechanistically, CML modulates phosphorylation of PI3K/AKT signalling pathways and modulates downstream apoptotic proteins P53, Bax, Bad, Bcl-2, cytochrome-c, caspase-3 and DFF-40. Overall, the study reports the immunomodulatory lectin in Cordia myxa with its potential therapeutic role. CML targets PI3K/AKT signalling mediated apoptosis to regress both in-vitro and in-vivo tumour. [Display omitted] •Wild Edible fruit Cordia myxa was screened for immunostimulatory lectin.•Protein purification profile identified ̴12 kDa Lectin from Cordia myxa (CML) and it is characterized.•CML mediated immunomodulation induces antiproliferative activity by inducing apoptosis in both in-vitro and in-vivo.•CML targets PI3K and AKT phosphorylation and modulates downstream apoptosis profile to induce antineoplastic activity.