Sains Malaysiana 51(3)(2022): 815-822

http://doi.org/10.17576/jsm-2022-5103-15

Malaysian Tualang Honey Suppresses the Angiogenic Events in Endothelial Cells Induced by Vascular Endothelial Growth Factor

(Madu Tualang Malaysia Menindas Keadaan Angiogenik dalam Sel Endotelium Teraruh oleh Faktor Pertumbuhan Endotelium Vaskular)

AHMAD FIRDAUS BIN ABDUL KHALID¹, CHIN THENG NG², LAI YEN FONG³, JUN JIE TAN⁴, FAHMI BIN YAKOP⁵, NUR AQILAH BINTI KAMARUDDIN¹, MUHAMMAD NAZRUL HAKIM ABDULLAH⁶ & YOKE KEONG YONG^1,*

¹Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

  ²Unit of Physiology, Faculty of Medicine, AIMST University, 08100 Bedong, Kedah Darul Aman, Malaysia

  ³Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, 43000 Kajang, Selangor Darul Ehsan, Malaysia

  ⁴Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia

  ⁵Department of Basic Sciences and Oral Biology, Faculty of Dentistry, Universiti Sains Islam Malaysia, 55100 Kuala Lumpur, Federal Territory, Malaysia

  ⁶Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

Diserahkan: 15 April 2021/Diterima: 3 Ogos 2021

Abstract

Anti-VEGF therapy has been used as the anti-angiogenic agent in cancer treatment. However, the treatment often couples with severe complications. Complementary natural products that offer similar anti-angiogenic potency with less side effects are sought as alternatives. Study showed that Malaysian Tualang Honey (MTH) can inhibit inflammation-induced vascular hyperpermeability in vitro and in vivo, but the effect on the angiogenesis process remains unclear. Thus, this study aims to determine the anti-angiogenic effects of MTH. Effects of MTH ranging from 0.3% to 0.9% on VEGF-induced human umbilical vein endothelial cells (HUVEC) angiogenesis was determined by proliferation, migration and tube-formation assays. Matrix metalloproteinase-2 (MMP-2) secretion from HUVEC and VEGF production from MCF7 cancer cells in response to MTH were also quantified by using ELISA kits. Suramin, an angio-suppressive agent was used as positive control. MTH significantly suppressed HUVEC proliferation (from 155% proliferation rate to 54%); migration (~ 50% inhibition rate) and tube-formation (69% reduction) induced by VEGF. These findings were explained by the significant reduction (p < 0.05) of VEGF-induced MMP-2 secretion in HUVEC with 39% suppression exhibited by 0.9% of MTH. MTH also significantly (p < 0.05) reduced VEGF secretion (19% reduction compared to control) in MCF7 breast cancer cells. Our findings suggest that the anti-angiogenic effects of MTH mainly targets endothelial cell through inhibition cell proliferation, migration and tube formation capacity, via suppression of MMP-2 secretion by the endothelial cells. However, MTH has less prominent effect on suppressing VEGF secretion by the MCF7 cancer cells.

Keywords: Angiogenesis; human umbilical veins endothelial cells; matrix metalloproteinases-2; migration; proliferation; tube formation

Abstrak

Terapi anti-VEGF telah digunakan sebagai agen anti-angiogenik dalam rawatan kanser. Walau bagaimanapun, rawatan ini menyebabkan komplikasi yang teruk. Produk pelengkap semula jadi yang memberikan potensi anti-angiogenik serupa dengan kurang kesan sampingan dicari sebagai alternatif. Kajian menunjukkan bahawa Madu Tualang Malaysia (MTH) boleh menghalang kebolehtelapan vaskular yang disebabkan oleh keradangan secara in vitro dan in vivo, tetapi kesan ke atas proses angiogenesis masih kurang jelas. Oleh itu, kajian ini bertujuan untuk menentukan kesan anti-angiogenik MTH. Kesan MTH antara 0.3% hingga 0.9% pada angiogenesis sel endotelium vena umbilikus manusia (HUVEC) yang disebabkan oleh VEGF telah ditentukan melalui ujian percambahan, penghijrahan dan pembentukan tiub. Rembesan matriks netaloproteinase-2 (MMP-2) daripada pengeluaran HUVEC dan VEGF daripada sel kanser MCF7 sebagai tindak balas kepada MTH juga dihitung dengan menggunakan kit ELISA. Suramin, agen penekan angio digunakan sebagai kawalan positif. MTH telah menyekat percambahan HUVEC teraruh VEGF dengan ketara (daripada 155% kadar percambahan kepada 54%); penghijrahan (~ 50% kadar perencatan) dan pembentukan tiub (69% pengurangan). Penemuan ini dijelaskan oleh pengurangan ketara (p <0.05) rembesan MMP-2 yang disebabkan oleh VEGF dalam HUVEC dengan 39% penindasan ditunjukkan oleh 0.9% daripada MTH. MTH juga secara signifikan (p <0.05) mengurangkan rembesan VEGF (pengurangan 19% berbanding kawalan) dalam sel kanser payudara MCF7. Penemuan ini mencadangkan bahawa kesan anti-angiogenik MTH mensasarkan sel endotelium secara utama dengan percambahan sel perencatan, penghijrahan dan kapasiti pembentukan tiub, melalui penindasan rembesan MMP-2 oleh sel endotelium. Walau bagaimanapun, MTH mempunyai kesan yang kurang menonjol dalam menyekat rembesan VEGF oleh sel-sel kanser MCF7.

Kata kunci: Angiogenesis; sel endotelium urat umbilikus manusia; matriks metaloproteinase-2; penghijrahan; percambahan; pembentukan tiub

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^*Pengarang untuk surat-menyurat; email: yoke_keong@upm.edu.my