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<p>Though Mica has been used for dysentery, bleeding and inflammation in Ayurveda medicine along with recent evidence on antimicrobial and antitumor effect, the underlying antitumor mechanism of Mica is not fully understood to date. Thus, the antitumor mechanism of processed Mica (PMC) was explored in non-small cell lung cancer cells. Herein PMC showed cytotoxicity and increased sub G1 population in H460 and A549 non-small cell lung cancer cells (NSCLCs). Also, PMC attenuated the expression of pro-PARP, pro-Caspase 3, cdk2, Cyclin A, NRF2, β-catenin, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc and s-phase kinase-associated protein 2 (Skp2) compared to untreated control in H460 and A549 cells. Interestingly, CNOT2 was highly expressed at mRNA level in tumor tissues more than in normal tissues with poor prognosis in the patients with lung cancer. Also, TCGA reveals that CNOT2 closely interacts with c-Myc with spearman score of 0.28. Consistently, CNOT2 was bound to c-Myc in H460 cells by Immunoprecipitation and CNOT2 overexpression disturbed the ability of PMC to reduce c-Myc in A549 cells. Also, PMC significantly increased production of reactive oxygen species (ROS) in H460 and A549 cells. Conversely, ROS inhibitor, N-acetyl-<span>l</span>-cysteine (NAC), disturbed the capacity of PMC to reduce pro-PARP, pro-caspase 3, CNOT2 and c-Myc in A549 cells. Furthermore, PMC showed synergistic apoptotic potential with doxorubicin in H460 cells compared to doxorubicin alone by using CompuSyn analysis and SynergyFinder. Overall, these findings suggest that PMC induces apoptosis in lung cancers via inhibition of CNOT2/c-Myc and production of ROS with combinatorial potential with doxorubicin.</p>

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Apoptotic and combinatorial potential of processed Mica via inhibition of CCR4-NOT transcription complex subunit 2/c-Myc and production of reactive oxygen species in non-small cell lung cancer cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Woohee Park,
  • Su-Yeon Park,
  • Deok Yong Sim,
  • Bum-Sang Shim,
  • Bonglee Kim,
  • Sung-Hoon Kim

摘要

Though Mica has been used for dysentery, bleeding and inflammation in Ayurveda medicine along with recent evidence on antimicrobial and antitumor effect, the underlying antitumor mechanism of Mica is not fully understood to date. Thus, the antitumor mechanism of processed Mica (PMC) was explored in non-small cell lung cancer cells. Herein PMC showed cytotoxicity and increased sub G1 population in H460 and A549 non-small cell lung cancer cells (NSCLCs). Also, PMC attenuated the expression of pro-PARP, pro-Caspase 3, cdk2, Cyclin A, NRF2, β-catenin, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc and s-phase kinase-associated protein 2 (Skp2) compared to untreated control in H460 and A549 cells. Interestingly, CNOT2 was highly expressed at mRNA level in tumor tissues more than in normal tissues with poor prognosis in the patients with lung cancer. Also, TCGA reveals that CNOT2 closely interacts with c-Myc with spearman score of 0.28. Consistently, CNOT2 was bound to c-Myc in H460 cells by Immunoprecipitation and CNOT2 overexpression disturbed the ability of PMC to reduce c-Myc in A549 cells. Also, PMC significantly increased production of reactive oxygen species (ROS) in H460 and A549 cells. Conversely, ROS inhibitor, N-acetyl-l-cysteine (NAC), disturbed the capacity of PMC to reduce pro-PARP, pro-caspase 3, CNOT2 and c-Myc in A549 cells. Furthermore, PMC showed synergistic apoptotic potential with doxorubicin in H460 cells compared to doxorubicin alone by using CompuSyn analysis and SynergyFinder. Overall, these findings suggest that PMC induces apoptosis in lung cancers via inhibition of CNOT2/c-Myc and production of ROS with combinatorial potential with doxorubicin.